Invariant Valpha7.2-Jalpha33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells.
The anti-tumor response of human invariant NKT (NKT) cells is well established. A novel T cell subset, mucosal-associated invariant T (MAIT) cells, possesses similar regulatory properties to NKT cells in autoimmune models and disease. Here, we examined the clonality of four T cell subsets expressing invariant alphaTCR, including Valpha7.2-Jalpha33 of MAIT cells, in 19 kidney and brain tumors. The MAIT clonotype was identified and co-expressed with NKT clonotype in half of the tumors. In contrast, two other invariant T cell clonotypes (Valpha4 and Valpha19) were not present in tumors. Such tumors also expressed Vbeta2 and Vbeta13, the restricted TCRbeta chain of MAIT cells and the antigen-presenting molecule MR1. A high percentage of infiltrating T cells was CD8+ and expressed HLA-DR suggesting activation. Although the MAIT alphaTCR was identified in both peripheral CD56+ and CD56- subsets, infiltrating lymphocytes were CD56 negative. The clonal presence of MAIT cells in tumors correlated with the expression of pro-inflammatory cytokines but no IL-4, IL-5 and IL-10, suggesting that a pro-inflammatory subset of human MAIT cells may exist. Our data imply that a CD56- subset of MAIT cells may participate in tumor immune responses similarly to NKT cells.
Peterfalvi
Agnes
A
Department of Neurology.
Gomori
Eva
E
Magyarlaki
Tamas
T
Pal
Jozsef
J
Banati
Miklos
M
Javorhazy
Andras
A
Szekeres-Bartho
Julia
J
Szereday
Laszlo
L
Illes
Zsolt
Z
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019002:CD56 Antigen / Q000096:biosynthesis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D019673:Genes, T-Cell Receptor alpha / Q000276:immunology; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018928:Immunity, Mucosal; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055611:Natural Killer T-Cells / Q000378:metabolism*; D018807:Polymorphism, Single-Stranded Conformational; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D019002:CD56 Antigen; D016207:Cytokines; D006684:HLA-DR Antigens